Among diseases collectively called arthropathy, as a typical disease in which degeneration such as color change, fibrillar feature or fissuring of articular cartilage is caused or articular cartilage is damaged, osteoarthritis such as knee osteoarthritis, hip osteoarthritis and spinal osteoarthritis, and traumatic arthropathy caused by a sport, an accident or the like are exemplified. In the diagnosis of such a disease, plain radiography is generally carried out, and the degree of progression of the disease is diagnosed by evaluating the status of joint space and the presence or absence of osteophyte or the like. However, there are some cases in which individuals complain of arthropathic symptoms such as pain or swelling although an abnormality is not found by plain radiography. Among such cases, by diagnosis through direct visual examination or arthroscopy, there are many cases in which damage to the ligament, tendon or other articular soft tissues is found, and there are cases in which mild degeneration or damage is found on the surface of articular cartilage associated with the tissues.
As described above, if arthroscopy is used, articular cartilage or articular soft tissue degeneration or damage which cannot be detected by radiography can be detected. However, a method using arthroscopy imposes a burden on a patient as compared with in vitro diagnosis and is not a widely used method.
As a component of proteoglycan that forms the extracellular matrix of articular cartilage, keratan sulfate (hereinafter referred to as “KS”) is contained, and therefore, an attempt has been made to detect a joint disease by using the KS concentration in blood, synovial fluid or the like as an index.
For example, Miyauchi et al. have proposed a method of detecting a joint disease comprising treating KS in synovial fluid with an enzyme (keratanase II) having an ability to hydrolyze the β-N-acetylglucosaminide linkage and measuring the produced Gal-GlcNAc (6S) (m-ks) by the HPLC method (Patent document 1). However, because in this method, synovial fluid is used as a sample, it is difficult to apply this method to diagnosis of arthropathy such as early knee osteoarthritis and hip osteoarthritis in which accumulation of synovial fluid is not observed.
On the other hand, Thonar et al. have proposed a diagnostic method for an abnormality of cartilage tissue by measuring KS in serum based on the fact that when KS in serum was measured by an immunoassay method using a monoclonal antibody which reacts with KS and the KS concentration in serum was abnormally high in the cases of osteoarthritis, and have also described the serum KS concentration range showing an abnormality of cartilage tissue (Patent document 2). However, in Patent document 2, although it has been disclosed that the KS concentration tends to increase in a blood sample of a patient who has already received treatment of a joint disease, there has been no description or suggestion that articular cartilage degeneration or damage in a stage which cannot be detected in a radiograph can also be detected by measuring the KS concentration in a sample derived from blood. Further, there are many reports published thereafter that the KS concentration in serum is not useful as an index of articular cartilage degeneration. For example, Campion et al. concluded in 1991 from the experimental results of an immunoassay method using a monoclonal antibody which reacts with KS that the KS concentration in serum of a patient with knee osteoarthritis has a low correlation with the clinical symptoms of the patient or radiographic evaluation and the serum KS concentration cannot be used as an index of articular cartilage degeneration (Non-patent document 1).    Patent document 1: JP-A-2001-57900    Patent document 2: JP-B-6-84971    Non-patent document 1: Campion G V. et al., Arthritis Rheum. 1991; 34: 1254-9